Biochemical and microscopic evidence for the internalization and degradation of heparin-containing mast cell granules by bovine endothelial cells.

Incubation of [35S]heparin-containing mast cell granules with cultured bovine endothelial cells was followed by the appearance of 35S-granule-associated radioactivity within the endothelial cells and a decrease in radioactivity in the extracellular fluid. These changes occurred during the first 24 hours of incubation and suggested ingestion of the mast cell granules by the endothelial cells. Periodic electron microscopic examination of the monolayers confirmed this hypothesis by demonstrating apposition of the granules to the plasmalemma of endothelial cells, which was followed by the engulfment of the granules by cytoplasmic projections. Under light microscopic examination, mast cell granules within endothelial cells then appeared to undergo degradation. The degradation of [35S]heparin in mast cell granules was demonstrated by a decrease in the amount of intracellular [35S]heparin proteoglycan after 24 hours and the appearance of free [35S]sulfate in the extracellular compartment. Intact endothelial cells were more efficient at degrading [35S]heparin than were cell lysates or cell supernatants. These data provide evidence of the ability of endothelial cells to ingest mast cell granules and degrade native heparin that is presented as a part of the mast cell granule.